Process for the preparation of corroles and several such new compounds, including chiral derivatives, and the use thereof

ABSTRACT

A new process for the preparation of corroles, having the structure of formula I below relies on a solvent-free condensation of an aldehyde with a pyrrole. Further disclosed are several new corroles, salts, optically active isomers and complexes thereof synthesized using the process.

FIELD OF THE INVENTION

The present invention relates to a new process for the preparation ofcorroles and to a new class of corroles. The new class of corrolesincludes inter alia, water-soluble corroles and chiral corroles.

BACKGROUND OF THE INVENTION

The simplest corrole has the following structure:

As shown in the above formula, corroles are slightly contractedporphyrins. Porphyrins are tetrapyrroles. They consist of four pyrrolerings (which are weakly aromatic) joined by methene bridges in a cyclicconfiguration, to which a variety of side chains are attached.

The metal complexes of porphyrin derivatives are involved in the mostimportant biochemical processes, such as the binding and transportationof oxygen (the heme in myo- and hemoglobin), electron transfer (the hemein cytochromes), oxidation as part of biosynthesis and biodegradation(metabolism) of organic and inorganic compounds (heme-dependentenzymes), photosynthesis (magnesium chlorin in chlorophylls), and inVitamin B₁₂ (cobalamin, with a reduced cobalt corrole structure).Synthetic metal complexes of porphyrins are extensively utilized asoxidation catalysts, as well as for other catalytic transformations.Also, a numerous number of porphyrins and their metal complexes areconstantly tested for biomedical purposes, most notable for treatment ofcancer and AIDS.

Corroles are much less known than porphyrins and their synthesis is avery complicated matter (a) Sessler, J. L.; Weghorn, S. J. in Expanded,Contracted, & Isomeric Porphyrins, Pergamon, Oxford, 1997, pp. 1-503. b)Vogel, E. J. Heterocyc. Chem. 1996, 33, 1461. c) Licoccia, S.; Paolesse,R. Struct. Bond. 1995, 84, 71). The first corrole was reported in 1965,and although the synthetic methods were improved during the yearspassed, there is still no simple procedure for that purpose. In thisrespect, even in the single and recently reported one-pot corrolesynthesis (Ohyama, K.; Funasaki, N. Tetrahedron. Lett. 1997, 38, 4113),the dipyrrolic starting material is not commercially available and isalso quite unstable. Because of the severe difficulties in thepreparation of corroles, their potential in the fields where porphyrinswere proven to be highly efficient was never explored.

OBJECTS OF THE INVENTION

It is an object of the present invention to provide a new and simpleprocess for the preparation of corroles, starting from relatively simpleand commercially available starting materials.

It is another object of the invention to provide novel corroles, theirsalts, optically active enantiomers and metal complexes thereof.

SUMMARY OF THE INVENTION

The synthetic approach relies on a one-pot, solvent-free condensation ofan aldehyde with a pyrrole. All starting materials are commerciallyavailable and stable at ambient conditions (temperature, air, humidity)and the reaction yields are reasonable, considering the complexity ofthe products.

The term “solvent-free” refers to a reaction carried out without anysolvent but may be performed with the aid of solid material, such aschromatographic supports or metal salts.

Thus, the present invention provides a process for the preparation ofcorroles of the following formula I:

wherein:

each R¹ is hydrogen or is selected from straight or branched C₁-C₁₂alkyl, aralkyl, aryl, heteroaryl, where any of these radicals may besubstituted;

R² and R³ are identical or different and each R² and each R³ representshydrogen or a radical selected from straight or branched C₁-C₁₂ alkyl,aralkyl, aryl, where any of these radicals may be substituted, and

R⁴, R⁵ and R⁶ are each hydrogen or represent identical or differentradicals selected from straight or branched C₁-C₁₂ alkyl, aralkyl, aryl,acyl, alkylsulfonyl or arylsulfonyl. where any of these radicals may besubstituted;

which process comprises solvent-free condensation of an aldehyde offormula II with a pyrrole of formula III

wherein R¹, R² and R³ are as defined above, followed by dehydrogenation,to obtain a compound of formula I wherein R⁴, R⁵ and R⁶ are hydrogen,

and if desired converting said compound of formula I to a compound offormula I wherein at least one of R⁴, R⁵ or R⁶ is other than hydrogen,

and if desired converting any compound obtained into a salt or a metalcomplex.

Further disclosed are several new compounds of formula I, salts andmetal complexes thereof. Also provided are optically pure enantiomers ofthese novel compounds. The metal complexes of the compounds of formula Iwere found to behave as very efficient catalysts in synthesis, forexample in cyclopropanation or oxidation of hydrocarbons and in thealkylation of electrophilic derivatives. Some of the new corroles areeasily converted into water-soluble derivatives, such feature beingcrucial for exploring certain potential applications.

DETAILED DESCRIPTION OF THE INVENTION

As stated above, one object of the present invention is to provide a newprocess for the preparation of corroles, the main advantages of whichare listed below:

1. The synthetic procedure is a one-pot synthesis.

2. All starting materials are simple and commercially available.

3. The amount of chemicals, other than those which are absolutelyrequired as the basic building blocks of the final material, is heavilyreduced compared to all other known methods.

The new corroles which were prepared by the novel process described inthis invention may be described by the general formula I:

wherein

each R¹ hydrogen or is selected from straight or branched C₁-C₁₂ alkyl,aralkyl, aryl, or heteroaryl, where any of these radicals may besubstituted,

R²and R³ are each hydrogen, and

R⁴, R⁵ and R⁶ are each hydrogen, or one of them may represent a radicalselected from straight or branched C₁-C₁₂ alkyl, aralkyl, aryl, carboxylor sulfonyl, where any of these radicals may be substituted.

The R¹ group may have, for example the following meanings:2,3,4,5,6-pentafluorophenyl; 2,6-difluorophenyl; 2,6-dichlorophenyl;4-(2-pyridyl)-2,3,5,6-tetrafluorophenyl and 4-(N-methyl-2-pyridyliumiodide)-2,3,5,6-tetrafluorophenyl. Several new corroles which wereprepared by the process of the present invention are shown in thefollowing formulae 1-9 in Scheme 1:

Other examples of new corroles according to the present invention arechiral corroles wherein one of the protons attached to the nitrogen inthe pyrrole ring is replaced by a substituent, as for example an alkyl,alkylaryl, aryl, aralkyl, carboxy, or sulfuryl group. These chiralcorroles may be represented by formulae IV and V as follows:

wherein R¹ is as defined above and R has the same meanings as given foreither of R⁴, R⁵ and R⁶ above. The structures shown in formulae IV and Vrepresent the N(21)- and N(22)-substituted corroles, respectively. Bothstructures are chiral and can be resolved into enantiomers bycrystallization in the presence of an enantiomerically pure acid.

The metal complexes of the corroles of formula I were found to behave asefficient catalysts. The structures of some novel metallocorrolesaccording to the present invention are shown in Scheme 2 below:

The following equations show potential uses of metallocorroles ascatalysts in organic synthesis, for example in epoxidation orcyclopropanation reactions:

In reaction (2) above X might be either a non chiral substituent such asfor example an EtO— group or a chiral substituent such as (+) or(−)2,10-camphorsultam.

The chiral corroles of the present invention, such as for examplecompounds 6-9 shown in Scheme 1 above, also exhibit catalytic effect onthe addition of diethylzinc to aldehydes:

The substituent R may be a group selected from straight or branchedC₁-C₁₂ alkyl, aralkyl, aryl, or heteroaryl.

The corroles of the present invention and the derivatives thereof suchas metal complexes) have unique properties which are relevant to ariousapplications. Potential applications are in the fields of organic dyesand inks, non linear optics (NLO), conducting material, sensors (pH,ions, oxygen, etc.), conversion of solar energy to chemical andelectrical energies.

The most potential applications of the corroles of the invention andtheir metal complexes are derived at least partially, from the followingfeatures:

1. The color of the corroles is highly sensitive to pH changes, as theneutral form is purple-red, while both the protonated (at pH<2) and thedeprotonated forms (at pH>7) are intense-green.

2. A prerequisite for NLO and other applications which are based onmolecules with a permanent dipole is the synthesis of asymmetricallysubstituted compounds. The advantage of the corroles in this context, isin view of the fact that their less symmetric structure (point symmetryof C_(2v), like water) has an intrinsic polarity.

3. Properties as for example, conductivity, photoconductivity,photoluminescence, etc. are based on strong intermolecular interactions.The preliminary results with the iron and copper complexes of thecorroles show that this interaction is stronger than in porphyrins.Thus, the corrole-corrole interactions in the μ-oxo dimer (1)₂(Fe)₂Oshown in Scheme 2 are much stronger than in analogous porphyrin dimers.

4. The water-soluble derivatives of corroles, such as compound 5 shownin Scheme 1, undergo pH-dependent protonation and deprotonationprocesses in water.

The present invention will be described in more detail with the aid ofthe following non-limiting examples.

EXAMPLE 1 Preparation of5,10,15-tris(2,3,4,5,6-pentafluorophenyl)corrole (1)

i) Solvent-free: from pyrrole and aldehyde

A solid absorbent (florisil, silica or alumina) (0.5 g) was mixed in a50 mL flask with a 2 mL CH₂Cl₂ solution of 0.31 mL (2.5 mmol) of2,3,4,5,6-pentafluorobenzaldehyde and 0.17 mL pyrrole (2.5 mmol), andthe solvent was distilled at normal pressure. The condenser was removedand the solid mixture was heated to 100° C., upon which the colorchanged to black within 5-10 min. After heating for 4 h, the solidsupport was washed with 50 mL CH₂Cl₂, 0.25 g (1.1 mmol) DDQ was added,and the product was purified by chromatography on silica gel withhexane:CH₂Cl₂ (9:1) as eluent. The isolated chemical yield of 1 was 11%.

Compounds 5,10,15-tris(2,6-difluorophenyl)corrole (2) and5,10,15-tris(2,6-dichlorophenyl)corrole (3) were prepared in a similarmanner from the corresponding benzaldehydes, to give 6%, and 1% yields,respectively.

When the reaction between pyrrole and 2,3,4,5,6-pentafluorobenzaldehydewas carried out in the absence of any solid support but under the samereaction conditions and the same work-up procedure, compound (1) wasformed and the yield was 5%. When the same reaction was performed atroom temperature, the yield was 8-11%.

ii) In solution: from pyrrole, 2,2′bipyrrole, and aldehyde (in a ratioof 1:2:3)

A mixture of 2.5 mmol of 2,2′-bipyrrole (prepared in two steps frompyrrole and 2-pyrrolidinone in 30% yield. and freshly sublimed), 5 mmolof pyrrole and 7.5 mmol of the substituted benzaldehyde in 500 mL CHCl₃was heated to reflux under a nitrogen atmosphere and 3.3 mmol ofBF₃—OEt₂ was added. After 1 h, 7.5 mmol of DDQ were added and thereaction was heated for an additional 1 h. After cooling, 3.3 mmol oftriethylamine was added and the solvent was evaporated. The isolatedchemical yields of 1 and 3 after column chromatography were 3.3% and2.2%, respectively.

1: UV-vis (CH₂Cl₂): λ_(max) nm (ε×10³) 408 (114.0), 560 (17.6), 602(9.3). ¹H NMR (CDCl₃): 9.10 (d, J=4.4 Hz, 2H), 8.75 (d, J=4.4 Hz, 2H),8.57 (d, J=4.4 Hz, 4H), −2.25 (bs, 3H). ¹⁹F NMR (CDCl₃): −137.55 (dd,J¹=24.2 Hz, J²=8.1 Hz, 2F), −138.14 (dd, J¹=23.03 Hz, J²=6.9 Hz, 4F),−152.52 (t, J=19.6 Hz, 2F), −153.10 (t, J=20.7 Hz, 1F), −161.78 (dt,J¹=24.2 Hz, J²=8.1 Hz, 4F), −162.35 (dt, J¹=23.03 Hz, J²=6.9 Hz, 2F).HRMS⁺ (e/z) 797.085466, (calculated for C₃₇H₁₂N₄F₁₅: 797.082245).

2: UV-vis (CH₂Cl₂): λ_(max) nm (ε×10³) 406 (118.6), 562 (20.3), 602(11.9). ¹H NMR (CDCl₃): 8.99 (d, J=4.3 Hz, 2H), 8.71 (d, J=4.3 Hz, 2H),8.52 (t, J=4.3 Hz, 4H), 7.72 (m, 3H), 7.33 (m, 6H), −2.1 (bs, 3H). ¹⁹FNMR (CDCl₃): d −109.32 (t, J=6.4 Hz, 2F), −109.75 (t, J=6.4 Hz, 4F).HRMS⁺ (e/z) 635.166000 (calculated for C₃₇H₂₁N₄F₆: 635.167041).

3: UV-vis (CH₂Cl₂): λ_(max) nm (ε×10³) 408 (106.1), 422 (86.6), 560(16.7), 604 (9.3). ¹H NMR (CDCl₃): 8.91 (d, J=4.2 Hz, 2H), 8.49 (d,J=4.8 Hz, 2H), 8.35 (d J=4.6 Hz, 4H), 7.72 (m, 3H), 7.33 (m, 6H), −1.7(bs, 3H). MS⁺ (e/z) 732.1 (MH⁺, 100%), MS⁻ (e/z) 730.7 ([M−H]⁻, 100%).HRMS⁺ (e/z) 729.981913 (calculated for C₃₇H₂₀N₄Cl₆: 729.981000)

EXAMPLE 2 Preparation of5,10,15-tris(4-(2-pyridyl)-2,3,5,6-tetrafluorophenyl)corrole (4)

0.42 mL of an 1.6 M n-BuLi solution (0.7 mmol) was added to a stirredsolution of 0.054 mL (0.56 mmol) 2-bromopyridine in 6 mL of dry THFunder an argon atmosphere at −78° C., at such a rate that thetemperature of the mixture did not exceed −70° C. After the addition wascomplete, the reaction mixture was stirred for 1 h at −78° C., to give aclear yellow solution. Next, a solution of 0.03 g (0.038 mmol)5,10,15-tri(2,3,4,5,6-pentafluorophenyl)corrole (1) in 6 mL of dry THFwas added dropwise. The mixture was stirred for 1 h at −78° C. and thenhydrolyzed with saturated aqueous bicarbonate solution. The layers wereseparated, the aqueous layer washed with ether, and the combined etherextracts were dried and evaporated to a solid residue.

The product was purified by column chromatography on silica gel (1:1EtOAc:Hexane) and recrystallized from CH₂Cl₂:Hexane to give 13 mg (35%yield) of the pure product as violet crystals.

UV-vis (CH₂Cl₂): λ_(max) nm 414 (111.6), 564 (18.4), 606. ¹H NMR(CDCl₃): 9.12 (d, J=3.9 Hz, 2H), 8.93 (m, 5H), 8.73 (d, J=4.88 Hz, 2H),8.66 (d, J=3.91 Hz, 2H), 8.00 (dt, J¹=7.81 Hz, J²=1.95 Hz, 3H), 7.84(bd, J=7.81 Hz, 3H), 7.51 (dt, J¹=6.84 Hz, J²=1.95 Hz, 3H), −2.02 (bs,3H). ¹⁹F NMR (CDCl₃): −138.19 (q, J=23.79 Hz, 2F), −138.81 (q, J=23.79Hz, 4F), −144.11 (q, J=23.79 Hz, 4F), −144.57 (q, J=23.79 Hz, 2F). MS⁺(e/z) 972.9 (MH⁺, 100%), MS⁻ (e/z) 972.7 ([M−H]⁻, 100%).

EXAMPLE 3 Preparation of 5,10,15-tris(4-(N-methyl-2-pyridyliumiodide)-2,3,5,6-tetrafluorophenyl)corrole (5)

A mixture of 11 mg (11 μmol) of5,10,15-tri(4-(2-pyridyl)-2,3,5,6-tetrafluorophenyl)corrole (4) preparedin Example 2 and 0.8 mL(13 mmol) of CH₃I in 2 mL of freshly distilledDMF was heated to 70° C. for 3 h. After evaporation of the solvent theproduct was recrystallized from MeOH:Ether to give 15.5 mg (98% yield)of the title compound as green solids.

UV-vis (MeOH): λ_(max) nm (ε×10³) 430 (76.2), 576 (10.9), 622 (17.8). ¹HNMR (DMSO-d₆): 9.49 (d, J=5.98 Hz, 3H), 9.16 (bm, 8H), 9.00 (t, J=8.54Hz, 3H), 8.75 (t, J=7.68 Hz, 3H), 8.51 (t, J=7.68 Hz, 3H), 4.68 (s, 3H),4.65 (s, 6H). ¹⁹F NMR (DMSO-d₆)): d −137.26(bm, 4F), −138.04 (bm, 6F),−138.60 (bm, 2F).

EXAMPLE 4 Preparation ofN(21)-benzyl-5,10,15-tri(2,3,4,5,6-pentafluorophenyl)corrole (6) andN(22)-benzyl-5,10,15-tri(2,3,4,5,6-pentafluorophenyl)corrole (7)

A solution of 46 mg (58 μmol)5,10,15-tri(2,3,4,5,6-pentafluorophenyl)corrole (1) in 30 ml of toluenewas heated to reflux in the presence of 0.16 g dry K₂CO₃ while 5 mL oftoluene was distilled out. After the solution reached RT, 70 μL (0.58mmol) of benzylbromide was added at once and the mixture heated toreflux for 4 h. After evaporation of the solvent, the products wereseparated by column chromatography on basic alumina (100:2Hexane:EtOAc). Two fractions were separated; 17 mg of 7 (33% yield,eluted first) and 21 mg of 6 (41% yield).

7: UV-vis (CH₂Cl₂): λ_(max) nm 428(soret), 520, 560, 590, 648. ¹H NMR(CDCl₃): 9.11 (t, J=4.28 Hz, 2H), 8.72 (d J=4.28 Hz, 1H), 8.64 (d J=4.28Hz, 1H), 8.59 (bs, 1H), 8.44 (d J=5.35 Hz, 1H), 8.28 (d J=4.28 Hz, 1H),7.96 (d J=5.35 Hz, 1H), 6.67 (t, J=7.5 Hz, 1H), 6.44 (t, J=7.5 Hz, 2H),4.35 (d, J=7.5 Hz, 2H), −2.99 (bs, 2H), −3.48 (d, J=14.99 Hz, 1H), −4.09(d, J=13.92 Hz, 1H). ¹⁹F NMR (CDCl₃): −137.43 (dt, J¹=24.87 Hz, J²=9.04Hz, 2F), −137.92 (dd, J¹=27.13 Hz, J²=9.04 Hz, 1F), −138.6 (bt, J=27.13Hz, 2F), −139.47 (bd, J=22.61 Hz, 1F), −152.22 (t, J=22.61 Hz, 1F),−152.64 (t, J=20.35 Hz, 1F), −153.10 (t, J=20.35 Hz, 1F), −161.9 (m,6F). HRMS⁺ (e/z) 887.123 (calculated for C₄₄H₁₈N₄F₁₅: 887.129196).

6: UV-vis (CH₂Cl₂): λ_(max) nm 414(soret), 572, 612. ¹H NMR (CDCl₃):8.80 (dd, J¹=4.28 Hz, J²=2.14 Hz, 1H), 8.72 (bd J=4.28 Hz, 1H), 8.59(m,3H), 8.39(d J=4.28 Hz, 1H), 8.27 (d J=4.28 Hz, 1H), 7.60 (d J=4.28 Hz,1H), 6.82 (t, J=7.5 Hz, 1H), 6.64 (t, J=7.5 Hz, 2H), 5.04 (d, J=7.5 Hz,2H), −2.03 (d, J=13.92 Hz, 1H), −2.34 (d, J=14.99 Hz, 1H) −3.07 (bs,2H). ¹⁹F NMR (CDCl₃): −137.15 (dd, J¹=27.6 Hz, J²=10.2 Hz, 1F), −137.52(dt, J¹=27.0 Hz,J²=9.8 Hz, 2F), −137.95 (dd, J¹=27.6 Hz, J²=9.8 Hz, 1F),−139.70 (d, J=22.8, 1F), −152.10 (t, J=22.0 Hz, 1F), −153.05 (t, J=22.4Hz, 1F), −153.43 (t, J=22.0 Hz, 1F), −161.7 (m, 2F), −162.2 (m, 4F).

EXAMPLE 5 Preparation ofN(21)-(2-pyridyl)-5,10,15-tris(2,3,4,5,6-pentafluorophenyl)corrole (8)and N(22)-(2-pyridyl)-5,10,15-tris(2,3,4,5,6-pentafluorophenyl)corrole(9)

These two compounds were prepared by essentially the same procedure asdescribed in Example 4 above, but using 2-picolyl chloride hydrochlorideinstead of benzylbromide. 24 mg (72% yield) of (8) (eluted first) and7.7 mg (23% yield) of (9) were obtained.

8: UV-vis (CH₂Cl₂): λ_(max) nm 412 (soret), 572, 614. ¹H NMR (CDCl₃):8.84 (d, J=4.88 Hz, 1H), 8.64 (bs, 1H), 8.52 (m, 3H), 8.33 (d, J=4.88Hz, 1H), 8.29 (d, J=4.88 Hz, 1H), 7.74 (d, J=4.88 Hz, 1H), 7.52 (d,J=3.66 Hz, 1H), 7.14 (t, J=7.32 Hz, 1H), 6.72 (t, J=7.32 Hz, 1H), 5.37(d, J=7.32 Hz, 1H), −1.70 (d, J=15.87 Hz, 1H), −1.88 (d, J=15.87 Hz,1H), −2.92(bs, 2H). ¹⁹F NMR (CDCl₃): −137.22 (m, 3F), −137.73 (d,J=22.61 Hz, 1F), −138.07 (d, J¹=22.61 Hz, J²=9.04, 1F), −140.01 (d,J=22.61 Hz, 1F), −152.25 (t, J=22.61 Hz, 1F), −153.09 (t, J=22.61 Hz,1F), −153.48 (t, J=22.61 Hz, 1F), −162.1 (m, 6F). MS⁺ (e/z) 887.8, MS−(e/z) 885.6.

9: UV-vis (CH₂Cl₂): λ_(max) nm 428 (soret), 518, 562,596, 650. ¹H NMR(CDCl₃): 9.12 (t, J=4.66 Hz, 2H), 8.70 (d, J=4.66 Hz, 1H), 8.63 (d,J=4.66 Hz, 1H), 8.58 (d, J=4.66 Hz, 1H), 8.44 (d, J=4.66 Hz, 1H), 8.29(d, J=4.66 Hz, 1H), 7.97 (d, J=4.66 Hz, 1H), 7.49 (d, J=5.59 Hz, 1H),6.93 (dt, J¹=8.39 Hz, J²=1.86 Hz, 1H), 6.56 (dt, J¹=5.59 Hz, J²=2.80 Hz,1H), 4.73 (d, J=7.45 Hz, 1H), −3.12 (bs, 2H), −3.28 (d, J=15.84 Hz, 1H),−3.94 (d, J=15.84 Hz, 1H). ¹⁹F NMR (CDCl₃): −137.56 (t, J=27.13 Hz, 3F),−138.64 (d, J=22.61 Hz, 1F), −138.88 (d, J=22.61 Hz, 1F), −139.72 (d,J=22.61 Hz, 1F), −152.23 (t, J=22.61 Hz, 1F), −152.68 (t, J=22.61 Hz,1F), −153.24 (t, J=22.61 Hz, 1F), −161.9 (m, 6F); MS⁺ (e/z) 887.8, MS−(e/z) 885.6.

EXAMPLE 6

Resolution of (7) into its Enantiomers

The addition of (1R)-(−)-10-camphorsulphonic acid to a CH₂Cl₂/hexanesolution of the racemic N(22)-substituted corrole 7 resulted in a majorthick crystalline form, together with some minute amounts of needle-likecrystals. The solubility of the two crystalline forms in hexane was verydifferent, practically none for the former and very high for the latter.Extensive washing of the solids with cold hexane afforded 6 in itsenantiomerically pure form. The extent of resolution was judged by NMRinvestigation of CDCl₃ solutions of 6 in the presence of(1R)-(−)-10-camphorsulphonic acid, as well as in the presence of achiral shift reagent.

EXAMPLE 7 Preparation of Metal Complexes of5,10,15-tris-(2,3,4,5,6-pentafluorophenyl)corrole

The following metal complexes of5,10,15-tris(2,3,4,5,6-pentafluorophenyl)corrole have been prepared:

1. The Iron Complexes of Corrole 1: 1-Fe(Cl) and (1)₂(Fe)₂O

A mixture of 20 mg (25 μmol) of5,10,15-tri(2,3,4,5,6-pentafluorophenyl)corrole (1) and 40 mg of FeCl₂(0.3 mmol) in 5 mL of freshly distilled DMF was heated to reflux for 1h. After evaporation of the solvent the mixture was dissolved in CH₂Cl₂and washed with 10% HCl. The product was recrystallized fromCH₂Cl₂:hexane to provide 18 mg (85% yield) of the (chloro)iron(IV)complex, 1-Fe(Cl).

1-Fe(Cl): UV-vis (CH₂Cl₂): λ_(max) nm (ε×10³) 370 (42.1), 398 (46.1),506, 606. ¹H NMR (CDCl₃) (RT): −2.73 (bs, 2H), −11.3 (bs, 2H), −35.11(bs, 2H). ¹H NMR (CDCl₃) (260 K): 0.18 (bs, 2H), −4.82 (bs, 2H), −15.35(bs, 2H), −44.24 (bs, 2H). ¹⁹F NMR (CDCl₃): −157.12 (bs, 2F), −160.77(bs, 1F), −162.04 (bs, 2F), −164.38 (bs, 1F), −166.54 (bs, 4F), −166.94(bs, 2F), −168.79 (bs, 1F), −169.43 (bs, 2F). HRMS⁺ (e/z) 849.996(calculated for C₃₇H₉N₄F₁₅Fe: 849.993709). MS⁺ (e/z) 884.1, 848.8 (MH⁺,100%), MS⁻ (e/z) 882.4, 847.5 ([M−H]⁻, 100%).

The diamagnetic Woxo complex of corrole 1, (1)₂(Fe)₂O, was obtained inquantitative yield by repeated washing of a solution of 1-Fe(Cl) inCH₂Cl₂ by aqueous NaOH.

(1)₂(Fe)₂O: UV-vis (CH₂Cl₂): λ_(max) nm 382 (soret), 544. ¹H NMR (CDCl₃)(RT): 7.07 (d, J=4.04 Hz, 4H), 6.78 (d, J=4 Hz, 4H), 6.50 (d, J=5.14 Hz,4H), 6.43 (d, J=5.14 Hz, 4H).

2. The Copper Complexes of Corrole 1: 1-Cu

A solution of 6 mg (7.5 μmol) of5,10,15-tri(2,3,4,5,6-pentafluorophenyl)corrole (1) in 0.3 mL pyridinewas warmed to 80° C. A solution of 4 mg (20 μmol) copper(II) acetate in0.3 mL pyridine was also warmed to 80° C. and was added in one portionto the corrole solution. After 10 min at 80° C., the solvent wasevaporated and the product was separated by column chromatography onsilica gel (2:1 hexane:CH₂Cl₂), to provide 1-Cu in quantitative yield.1-Cu exists as a Cu^(II) corrole radical (broad NMR signals due toparamagnetism) at RT and as a Cu^(III) corrole (sharp NMR signals,diamagnetic) at low temperatures.

1-Cu: UV-vis (CH₂Cl₂): λ_(max) nm 404 (soret), 542. ¹H NMR (CDCl₃) (RT):7.95 (bs, 2H), 7.34 (bs, 2H), 6.99 (bs, 4H). ¹H NMR (CDCl₃) (240 K):7.94 (d, J=4.55 Hz, 2H), 7.49 (d, J=4.55 Hz,2H), 7.18 (s, 4H). ¹⁹F NMR(CDCl₃): d −137.11 (d, J=17.8 Hz, 4F), −137.97 (d, J=17.4 Hz, 2F),−152.26 (dt, J¹=22.2 Hz, J²=8.8 Hz, 3F), −160.91 (t, J=22.2 Hz, 6F).

3. The Manganese Complex of Corrole 1: 1-Mn

This complex was prepared by essentially the same procedure as describedfor 1-Fe(Cl), but using manganese(II) acetate tetrahydrate instead ofFeCl₂. The product was obtained in quantitative yield. Recrystallizationfrom EtOH/water afforded 1-Mn as a green solid.

1-Mn: MS (CI⁺, isobutane) 848 ([M⁺], 100%), 904 ([M⁺+C₄H₈], 80%), 906([M⁺+C₄H₁₀], 20%): UV-vis (CH₂Cl₂): λ_(max) nm 398, 414 (Soret), 478,596. ¹H NMR (pyridine-d₅, RT): 21.0 (s, 2H), 19.0 (bs, 2H), −17 (bs,2H), −42 (bs, 2H). ¹⁹F NMR (pyridine-d₅, RT): −117.5 (bs, 2F), −128.9(bs, 4F), −152.3 (s, 1F), −154.2 (s, 2F), −158.1 (s, 2F), −159.0 (s,4F). UV-vis (pyridine): λ_(max) nm 396, 418, 432, 488, 600. ¹H NMR(pyridine-d₅, RT): −4.0 (s, 2H), −19.0 (bs, 4H), −32.0 (bs, 2H). ¹⁹F NMR(pyridine-d₅, RT): −125.4 (bs, 4F), −139.0 (bs, 2F), −155.1 (s, 1F),−156.1 (s, 2F), −161.2 (s, 4F), −162.0 (s, 2F).

4. The Cobalt Complex of Corrole 1, 1-Co(PPh₃)

this complex was prepared in quantitative yields by succesive additionof 10.5 mg (13 μmol) 1, 10.8 mg NaOAc (130 μmol), 17.3 mg (67 μmol)PPh₃, and 16.4 mg (67 μmol) of Co(OAc)₂.4H₂O into 10 mL of ethanol,stiring at room temperature for 30 minutes, followed by evaporation ofthe solvent and flash-chromatography (CH₂Cl₂/hexanes).

1-Co(PPh₃): UV-vis (CH₂Cl₂): λ_(max) nm 376, 408 (soret), 548, 584. ¹HNMR (CDCl₃): 8.69 (d, J=4.4 Hz, 2H), 8.33 (d, J=4.8 Hz, 2H), 8.23 (d,J=4.8 Hz, 2H), 8.08 (d, J=4.6 Hz, 2H), 7.00 (td, J¹=7.7 Hz, J²=1.9 Hz,3H), 6.64 (td, J¹=8.0 Hz, J²=2.2 Hz, 6H), 4.57 (dd, J¹=11.3 Hz, J²=7.9Hz, 6H). ¹⁹F NMR (CDCl₃): −137.16 (dd, J¹=24.6 Hz, J²=8.1 Hz, 2F),−137.48 (dd, J¹=26.7 Hz, J²=9.2 Hz, 1F), −138.49 (dd, J¹=24.3 Hz, J²=8.3Hz, 2F), −138.78 (dd, J¹=24.0 Hz, J²=9.0 Hz, 1F), −154.07 (t, J=21.1 Hz,3F), −162.0-−162.9 (m, 6F).

5. The Pyridinium Salt of the Pd(II) Complex of 1: [1-Pd(pyr)]⁻pyrH⁺

A solution of 6 mg (7.5 μmol) of5,10,15-tri(2,3,4,5,6-pentafluorophenyl)cofrole (1) in 0.5 mL pyridinewas treated with 1.9 mg (8.5 μmol) Palladium(II) acetate. The mixturewas heated to 100° C. for 3 h and then hexane was slowly added untilcrystallization began. After filtration, 6.5 mg of the pyridinium saltof the palladium complex was obtained (95% yield).

UV-vis (CH₂Cl₂): λ_(max) nm 380,412,440,550,584. ¹H NMR (CDCl₃): 8.69(d, J=5.59 Hz, 2H), 8.62 (d, J=4.12 Hz, 2H), 8.32 (d, J=4.11 Hz, 2H),8.16 (d, J=4.34 Hz, 2H), 8.11 (d, J=3.97 Hz, 2H), 7.77 (t, J=7.47 Hz,1H), 7.33 (t, J=6.71 Hz, 2H), 7.06 (bs, 1H), 5.99 (bs, 2H), 3.19 (bs,2H). ¹⁹F NMR (CDCl₃): −136.6 (bm, 4F), −140.66 (bm, 2F), −154.94 (bm,3F), −162.5 (bm, 4F), −164.05(bm, 2F).

EXAMPLE 8

Catalysis

a) Epoxidation

1-Fe(Cl):Iodosylbenzene:Nitrobenzene:Styrene=1:100:100:1000.

0.32 mg (0.36 μmol): 8.5 mg (36 μmol): 3.7 mL (36 μmol): 41 mL (360μmol)

The epoxidation was complete after 3.5 h, with a chemical yield of 87%(66% styrene oxide, 21% of phenyl acetaldehyde).

Similar results were obtained with 1-Mn as catalyst.

b) Hydroxylation

Ethylbenzene:Iodosylbenzene:1-Fe(Cl)=1000:100:1

61 μL (0.5 mmol), 11 mg (0.05 mmol), 0.5 mg (0.5 μmol), in 1 mL benzene.

The reaction was stirred overnight at RT, after which phenethyl alcoholand acetophenon were obtained in a 2.5:1 ratio, with a 20% yield.Similar results were obtained with 1-Mn as catalyst.

c) Cyclopropanation

1-Fe(Cl):EDA:Styrene=1:500:5000

1.3 mg (1.5 μmol): 78 μL (0.74 mmol): 0.85 μL (7.4 mmol)

The reaction was complete after 2 h and a 67 % yield of the cyclopropaneproducts was obtained, with a trans :cis ratio of 2.18. Similar resultswere obtained with 1-Co(PPh₃) but with longer reaction times.

d) Asymmetric Cyclopropanation

1-Fe(Cl):enantiopure (+)-diazosultam (see equation 2):styrene=1:200:2000

0.6 mg (0.7 μmol): 40 mg (0.14 mmol): 0.16 mL (1.4 mmol)

The reaction was stopped after 27 h, when only traces of the diazocompound remained unreacted. The cyclopropane products were obtained inhigh yield with a trans:cis ratio of 1.2. The trans- and cis-isomerswere obtained with 34% de (R,R) and 73% de (R,S), respectively.

e)Alkylation

To 2.2 mL solution of diethylzinc in hexane, 0.2 mL of benzaldehyde and2 mg of a mixture of compounds 6 and 7 was added. After 17 h, thereaction was quenched by the addition of a few drops of saturatedammonium chloride. Solvent extraction (CH₂Cl₂/H₂O), followed by dryingand evaporation of the organic solvent, and flash chromatography,resulted in the isolation of the addition product (1-phenyl-1-propanol)in 25% yield.

EXAMPLE 9 Synthesis of 5,10,15-tris(heptafluoropropyl)corrole

1.08 gr. (5 mmol) of heptafluorobutyraldehyde hydrate were mixed with0.35 ml (5 mmol) of pyrrole, and heated to 65-70° C. for 3 hours. Thebrown oil was dissolved in CH₂Cl₂, and oxidized by 0.5 gr DDQ at roomtemperature. Chromatographic separation on silica-gel, followed byrecrystallizations from CH₂Cl₂/hexane and from benzene/hexane, allowedthe isolation of the pure 5,10,15-tris(heptafluoropropyl)corrole inabout 1% yields.

TLC (Silica, CH₂Cl₂:n-hexane=1:2): R_(f)=0.75.

MS (DCI+, isobutane): 802.1 (M+, 100%), 782.2 (M+−HF, 20%), 764.1(M+−2F, 17%).

UV-Vis (CH₂Cl₂, λ_(max)): 412 (e=116540), 510, 548, 610.

¹H-NMR (CDCl₃): 9.40 (4H), 9.24 (2H), 9.14 (2H).

¹⁹F-NMR (CDCl₃, 188 MHz): −79.68 ppm (t, 9F, J=10.34 Hz), −83.28 (s,2F), −96 (very broad s), −121.05 (s, 2F), −122.76 (s, 4F).

What is claimed is:
 1. A process for the preparation of a compound of formula I or salts, optically active isomers and complexes thereof

wherein: each R¹ is a hydrogen or is selected from straight or branched C₁-C₁₂ alkyl, aralkyl, aryl and heteroaryl, R² and R³ are identical or different and each R² and each R³ represents hydrogen or a radical selected from straight or branched C₁-C₁₂ alkyl, aralkyl and aryl, and R⁴, R⁶ and R⁶ are each hydrogen or represent identical or different radicals selected from straight or branched C₁-C₁₂ alkyl, aralkyl, aryl, acyl, alkylsulfonyl and arylsulfonyl; which process comprises solvent-free condensation of an aldehyde of formula II with a pyrrole of formula III

wherein R¹, R² and R³ are as defined above, followed by dehydrogenation, to obtain a compound of formula I wherein R⁴, R⁵ and R⁶ are hydrogen.
 2. A process according to claim 1, wherein said condensation is carried out with heating.
 3. A process according to claim 1, wherein said condensation is optionally carried out in the presence of a solid substrate.
 4. A process according to claim 3, wherein said substrate is selected from silica, alumina and florisil.
 5. A process according to claim 1, wherein a compound of formula I wherein R⁴, R⁵ and R⁶ are each hydrogen is converted to a chiral compound of formula I wherein at least one of R⁴, R⁵ and R⁶ is other than hydrogen.
 6. A process according to claim 1, wherein R¹ is a group that forms either a positive or negative ion, so as to obtain a water-soluble compound of formula I.
 7. A compound of formula I including the salts, the optically active isomers and the metal complexes thereof

wherein each R¹ is selected from straight or branched C₁-C₁₂ alkyl, aralkyl, aryl and heteroaryl, R² and R³ are each hydrogen, and R⁴, R⁵ and R⁶ are each hydrogen, or at least one of them may represent a radical selected from straight or branched C₁-C₁₂ alkyl, aralkyl, aryl, acyl, alkylsulfonyl and arylsulfonyl.
 8. A compound of formula I in claim 7, wherein R¹ is an aryl group.
 9. A compound of formula I in claim 7, wherein two of R⁴, R⁵ and R⁶ represent hydrogen and the third represents straight or branched C₁-C₁₂ alkyl, aralkyl, aryl, carboxyl or sulfonyl, such a compound being in an enantiomerically pure form.
 10. A metal complex of a compound of formula I in claim 7 including dimeric species thereof.
 11. A catalyst comprising the metal complex according to claim
 10. 12. The catalyst according to claim 11, wherein the catalyst catalyzes at least one of a cyclopropanation, an oxidation or an alkylation of hydrocarbons.
 13. A process according to claim 2, wherein said condensation is optionally carried out in the presence of a solid substrate.
 14. The process according to claim 1, wherein at least one of R⁴, R⁵ or R⁶ of the compound of formula I is not hydrogen.
 15. The process according to claim 1, wherein the compound of formula I is converted into a salt or metal complex. 